Pubmed du 13/09/23

Pubmed du jour

1. Abdel-Haq M, Ojha SK, Hamoudi W, Kumar A, Tripathi MK, Khaliulin I, Domb AJ, Amal H. Effects of extended-release 7-nitroindazole gel formulation treatment on the behavior of Shank3 mouse model of autism. Nitric oxide : biology and chemistry. 2023.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral deficits such as abnormalities in communication, social interaction, anxiety, and repetitive behavior. We have recently shown that the Shank3 mutation in mice representing a model of ASD causes excessive nitric oxide (NO) levels and aberrant protein S-nitrosylation. Further, 10-day daily injections of 7-NI, a neuronal nitric oxide synthase inhibitor, into Shank3(Δ4-22) and Cntnap2((-/-)) mutant mice (models of ASD) at a dose of 80mg/kg reversed the manifestations of ASD phenotype. In this study, we proposed an extended release of 7-NI using novel drug system. Importantly, unlike the intraperitoneal injections, our new preparation of poly (sebacic acid-co-ricinoleic acid) (PSARA) gel containing 7-NI was injected subcutaneously into the mutant mice only once. The animals underwent behavioral testing starting from day 3 post-injection. It should be noted that the developed PSARA gel formulation allowed a slow release of 7-NI maintaining the plasma level of the drug at ∼45 μg/ml/day. Further, we observed improved cognitive memory and social interaction and reduced anxiety-like behavior in Shank3 mutant mice. This was accompanied by a reduction in 3-nitrotyrosine levels (an indicator of nitrative/nitrosative stress) in plasma. Overall, we suggest that our single-dose formulation of PSARA gel is very efficient in rendering a therapeutic effect of 7-NI for at least 10 days. This approach may provide in the future a rational design of an effective ASD treatment using 7-NI and its clinical translation.

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2. Cheung T, Li TMH, Lam JYT, Fong KH, Chiu LY, Ho YS, Tse AC, Li CT, Cheng CP, Beisteiner R. Effects of transcranial pulse stimulation on autism spectrum disorder: a double-blind, randomized, sham-controlled trial. Brain communications. 2023; 5(5): fcad226.

Transcranial pulse stimulation has been proven effective to improve cognition, memory and depressive symptoms of Alzheimer’s disease, but supporting evidence on other neurological diseases or neuropsychiatric disorders remains limited. This study aimed to investigate the effects of transcranial pulse stimulation on the right temporoparietal junction, which is a key node for social cognition for autism spectrum disorder, and to examine the association between transcranial pulse stimulation and executive and social functions. This double-blinded, randomized, sham-controlled trial included 32 participants (27 males), aged 12-17 years with autism spectrum disorder. All eligible participants were randomized into either the verum or sham transcranial pulse stimulation group, on a 1:1 ratio, based on the Childhood Autism Rating Scale screening score. Sixteen participants received six verum transcranial pulse stimulation sessions (energy level: 0.2-0.25 mJ/mm(2); pulse frequency: 2.5-4.0 Hz, 800 pulse/session) in 2 weeks on alternate days. The remaining 16 participants received sham transcranial pulse stimulation. The primary outcome measure included Childhood Autism Rating Scale score changes, evaluated by parents, from baseline to 3-month follow-ups. Secondary outcomes included a self-reported questionnaire responded to by parents and cognitive tests responded to by participants. A licensed mental health professional evaluated clinical global impression severity, improvement, efficacy and total score. Results revealed significant interactions in Childhood Autism Rating Scale and other secondary outcomes. Significant group and time effects were found in most secondary outcomes. Additionally, significant differences were found between the transcranial pulse stimulation and sham transcranial pulse stimulation groups in Childhood Autism Rating Scale and clinical global impression improvement and total score immediately after 2 weeks of transcranial pulse stimulation intervention (all P < 0.05), and effects were sustainable at 1- and 3-month follow-up, compared with baseline. The effect size of Childhood Autism Rating Scale (d = 0.83-0.95) and clinical global impression improvement (d = 4.12-4.37) were large to medium immediately after intervention and sustained at 1-month post-stimulation; however, the effects were reduced to small at 3-month post-stimulation (d = 2.31). These findings indicated that transcranial pulse stimulation over right temporoparietal junction was effective to reduce the core symptoms of autism spectrum disorder, as evidenced by a 24% reduction in the total Childhood Autism Rating Scale score in the verum transcranial pulse stimulation group. Additionally, the clinical global impression total score was reduced by 53.7% in the verum transcranial pulse stimulation group at a 3-month follow-up, compared with the baseline. Participants in the verum transcranial pulse stimulation group had shown substantial improvement at 1- and 3-month follow-ups, compared with baseline, although some of the neuropsychological test results were deemed statistically insignificant. Future replication of this study should include a larger sample derived from multi-nations to determine transcranial pulse stimulation as an alternative top-on treatment option in neuropsychiatry.

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3. Ciancone-Chama AG, Bonaldo V, Biasini E, Bozzi Y, Balasco L. Gene expression profiling in trigeminal ganglia from Cntnap2(-/-) and Shank3b(-/-) mouse models of autism spectrum disorder. Neuroscience. 2023.

Sensory difficulties represent a crucial issue in the life of autistic individuals. The diagnostic and statistical manual of mental disorders describes both hyper- and hypo-responsiveness to sensory stimulation as a criterion for the diagnosis autism spectrum disorders (ASD). Among the sensory domain affected in ASD, altered responses to tactile stimulation represent the most commonly reported sensory deficits. Although tactile abnormalities have been reported in monogenic cohorts of patients and genetic mouse models of ASD, the underlying mechanisms are still unknown. Traditionally, autism research has focused on the central nervous system as the target to infer the neurobiological bases of such tactile abnormalities. Nonetheless, the peripheral nervous system represents the initial site of processing of sensory information and a potential site of dysfunction in the sensory cascade. Here we investigated the gene expression deregulation in the trigeminal ganglion (which directly receives tactile information from whiskers) in two genetic models of syndromic autism (Shank3b and Cntnap2 mutant mice) at both adult and juvenile ages. We found several neuronal and non-neuronal markers involved in inhibitory, excitatory, neuroinflammatory and sensory neurotransmission to be differentially regulated within the trigeminal ganglia of both adult and juvenile Shank3b and Cntnap2 mutant mice. These results may help in disentangling the multifaced complexity of sensory abnormalities in autism and open avenues for the development of peripherally targeted treatments for tactile sensory deficits exhibited in ASD.

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4. Gemmell M, Walsh T, Sherby M, Imbeah A, Bono K, Baldenweck M, Gurnett C, Newland JG. Clusters of SARS-CoV-2 Infection Across Six Schools for Students with Intellectual and Developmental Disabilities. Infectious diseases and therapy. 2023.

INTRODUCTION: Individuals with intellectual and developmental disabilities are at increased risk for adverse outcomes from coronavirus disease 2019. Clusters of COVID-19 infections can be used to track SARS-CoV-2 transmission. This is particularly important in environments frequently used for individuals with intellectual and developmental disabilities, such as schools. The objective of this study was to compare the number of clusters of student and staff cases identified during three distinct periods (pre-Delta, Delta, and Omicron) of the COVID-19 pandemic. METHODS: Weekly COVID-19 testing occurred from November 23, 2020 to May 27, 2022 during three phases of the COVID-19 pandemic: pre-Delta, Delta, and Omicron. Structured interviews were conducted with positive cases to determine if they contracted COVID-19 in the school environment, and interviews with school administrators responsible for contact tracing determined school-based clusters. RESULTS: 160 cases of COVID-19 were identified and 55 cluster positives were recorded during the study period. 0 (0%) cluster positives were recorded during the pre-Delta variant wave, 3 (5%) cluster positives were recorded during the Delta variant wave, and 52 (95%) cluster positives were recorded during the Omicron variant wave. Additionally, 23 (85%) of all positives during pre-Delta, 12 (50%) of all positives during Delta, 66 (61%) of all positives during Omicron, and 36 (69%) of cluster positives during Omicron did not receive CDC-recommended dosages of the COVID-19 vaccine. CONCLUSION: The Omicron variant led to an increase in cluster-based transmission, and staying up to date with vaccination guidelines was crucial in limiting transmission. CLINICAL TRIAL REGISTRATION: Prior to enrollment, this study was registered at ClinicalTrials.gov on September 25, 2020 (identifier NCT04565509; titled « Supporting the Health and Well-being of Children with Intellectual and Developmental Disability During COVID-19 Pandemic »).

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5. Hart LC, Sirrianni J, Rust S, Hanks C. Predicting timely transfer to adult care in a cohort of autistic adolescents and young adults. PloS one. 2023; 18(9): e0289982.

BACKGROUND: The transition from pediatric to adult care is a challenge for autistic adolescents and young adults. Data on patient features associated with timely transfer between pediatric and adult health care are limited. Our objective was to describe the patient features associated with timely transfer to adult health care (defined as

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6. Hawthorne K, Loveall SJ. The Effects of Syntactic, Semantic, and Pragmatic Prominence on Pronoun Interpretation in Adults With Intellectual and Developmental Disabilities. Journal of speech, language, and hearing research : JSLHR. 2023; 66(9): 3606-21.

PURPOSE: Pronouns are referentially ambiguous: For example, « she » could refer to any female. Nonetheless, errors in pronoun interpretation rarely occur for adults with typical development (TD) due to several strategies implicitly shared between the talker and listener. The purpose of this study was to test the impacts of syntactic, semantic, and prosodic prominence on pronoun interpretation for adults with intellectual and developmental disabilities (IDD) and TD. METHOD: Adults with IDD (n = 28) and TD (n = 27) listened to ministories involving a pronoun with two potential antecedents that varied in syntactic, semantic, and pragmatic prominence. Subject/first-mentioned antecedents are more syntactically prominent than object antecedents. Semantic prominence was manipulated via verb transitivity: Subjects are more semantically prominent when the verb is highly transitive (e.g., « hit » vs. « see, » a low-transitivity verb for which the subject is merely experiencing the action). Pragmatic prominence was manipulated by placing prosodic focus on one of the two potential antecedents. Eye gaze to images representing the potential antecedents was tracked as a measure of online processing. Responses to a follow-up pronoun interpretation question were also recorded. RESULTS: Adults with TD used syntactic, semantic, and-in early processing-pragmatic prominence when interpreting ambiguous pronouns. Adults with IDD were sensitive to syntactic prominence but to a significantly lesser extent than their peers with TD. CONCLUSIONS: Pronouns are an integral part of everyday conversation, and when the conversational partners do not share common strategies to link ambiguous pronouns with their antecedents, misunderstandings will occur. Results show that adults with IDD only weakly share pronoun interpretation strategies with adults with TD, suggesting that pronouns may be an important focus for intervention for this population. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23875809.

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7. Javaheripour N, Wagner G, de la Cruz F, Walter M, Szycik GR, Tietze FA. Altered brain network organization in adults with Asperger’s syndrome: decreased connectome transitivity and assortativity with increased global efficiency. Frontiers in psychiatry. 2023; 14: 1223147.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that persists into adulthood with both social and cognitive disturbances. Asperger’s syndrome (AS) was a distinguished subcategory of autism in the DSM-IV-TR defined by specific symptoms including difficulties in social interactions, inflexible thinking patterns, and repetitive behaviour without any delay in language or cognitive development. Studying the functional brain organization of individuals with these specific symptoms may help to better understand Autism spectrum symptoms. METHODS: The aim of this study is therefore to investigate functional connectivity as well as functional network organization characteristics using graph-theory measures of the whole brain in male adults with AS compared to healthy controls (HC) (AS: n = 15, age range 21-55 (mean ± sd: 39.5 ± 11.6), HC: n = 15, age range 22-57 [mean ± sd: 33.5 ± 8.5]). RESULTS: No significant differences were found when comparing the region-by-region connectivity at the whole-brain level between the AS group and HC. However, measures of « transitivity, » which reflect local information processing and functional segregation, and « assortativity, » indicating network resilience, were reduced in the AS group compared to HC. On the other hand, global efficiency, which represents the overall effectiveness and speed of information transfer across the entire brain network, was increased in the AS group. DISCUSSION: Our findings suggest that individuals with AS may have alterations in the organization and functioning of brain networks, which could contribute to the distinctive cognitive and behavioural features associated with this condition. We suggest further research to explore the association between these altered functional patterns in brain networks and specific behavioral traits observed in individuals with AS, which could provide valuable insights into the underlying mechanisms of its symptomatology.

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8. Koum DCK, Enyama D, Foko LPK, Noukeu D, Nguedia B, Mbono R, Eposse C, Eboumbou PE, Engome CB, Mapoure YN. Diagnosis and treatment challenges of autism spectrum disorder at a reference hospital in Douala, Cameroon. BMC pediatrics. 2023; 23(1): 459.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disability associated with deficiency in social interaction, unusual development of social communication, and restricted or repetitive behaviors, interests and activities. This study aimed to describe management of pediatric ASD in Cameroon, a resource-constrained Central Africa country. METHODS: A retrospective study was conducted between December 2021 and May 2022 at the Pediatrics department of a reference hospital in the town of Douala. Data of interest of children with ASD were collected through eligible medical records and telephone discussions with their parents/guardians. RESULTS: Medical records of 145 children with ASD aged 2-15 years were included in the study, giving a hospital ASD prevalence of 3.7%. Time delay between parental concerns and hospital management was specified in 69 (47.58%) children, and among them 38 (55.07%) had a mean delay ± SD was less than five months. Children were mainly males (76%) and aged 4-5 years (37.93%), with mean age ± SD of 44.4 ± 22.2 months old. The main consultation reason was delayed language development (100%). Mean time delay between parental concerns and the first medical consultation was 18 months (range 1-60 month). Attention deficit hyperactivity disorder were found in 68.18% of children aged ≥ 6 years old. Neuropsychology (66.2%) was the most frequently used intervention. Some children were treated using traditional medicine. CONCLUSIONS: Management of pediatric ASD is strongly influenced by socioeconomic and cultural context. It is crucial to implement behavioral change campaigns in community, organize training sessions to medical staff on diagnosis and treatment of ASD, and provide specialized centers with skilled staff and equipped material.

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9. Nagda R, Le T, Lin B, Tanbonliong T. Oral hygiene practice and home-care challenges in children with autism spectrum disorder in San Francisco: Cross- sectional study. Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2023.

INTRODUCTION: Autism spectrum disorder (ASD) is characterized by challenges in social interaction, communication, and stereotypical patterns of behavior. They are more likely to have tooth brushing issues and need help with routine dental care. Children with ASD could face difficulty in accessing dental care as the parents have a challenging task in finding a dentist that would treat the child with special needs. As a result, dental care is often neglected. The aims of this study are to evaluate oral hygiene practices and challenges in children with ASD and compare it with typically developing peers (TDP). METHOD: The sample size of the study was 60. Parents of children aged 3-10 were recruited and divided in 2 groups with 30 in each group. Age and gender of children were matched. ASD group included children with medical diagnosis of ASD only and no other co-morbidities. Children in TDP group had no diagnosis of ASD, and reported no disability, or any other diagnosis. Parents were asked to complete the questionnaire which asked about their demographic information, child’s oral care regimens, and their knowledge about dental care. Chi-squared tests and t-test were used for statistical analysis. A p-value of .05 was used for determining statistical significance. RESULTS: Many children with ASD (47%) had to travel more than 20 miles for their dental home compared to 13% with TDP (p < .05). Only 60% of children with ASD brushed twice a day with 70% of parents reporting that it is difficult to brush their child's teeth compared to TDP with 93% of children brush twice daily (p < .05). Significantly a smaller number of children with ASD (47%) allowed their parent to brush their teeth as compared to 93% of TSD children (p < .001). CONCLUSION: Parents of children with autism spectrum disorder travel longer distance to find a dental home and face more difficulty in maintaining their child's daily oral hygiene.

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10. Wang Q, Ng SM, Zhou X. The mechanism and effectiveness of mindfulness-based intervention for reducing the psychological distress of parents of children with autism spectrum disorder: A protocol of randomized control trial of ecological momentary intervention and assessment. PloS one. 2023; 18(9): e0291168.

BACKGROUND: Existing studies have unequivocally demonstrated that parents of children with autism spectrum disorder (ASD) experience various stressful daily life events and suffer from psychological distress. Mindfulness level is found to be an effective buffer between parents’ appraisal of stress life events and psychological distress. However, the mechanism behind the function of mindfulness is unclear, and traditional mindfulness-based intervention (MBI) in experimental settings is not tailored to personal real-life needs. This study proposes to conduct a randomized controlled trial (RCT) to examine the effectiveness of MBI delivered by ecological momentary intervention (EMI) and assessed by ecological momentary assessment (EMA) in changing participants’ cognitive appraisal of stressful life events and thus reducing the psychological distress of parents of children with ASD. METHOD: The proposed study will recruit 670 parents of children with ASD and randomly assign them to the intervention and control groups (335 in each group). Participants in the intervention group will install the EMI/A app on their smartphones. In the app, participants can receive practice prompts daily, browse and practice different mindfulness exercises in the intervention library at any time, talk to a virtual counselor (chatbot) when feeling stressed, complete EMA on the cognitive appraisal of life events, and receive the log of change of psychological status daily. Participants in the control group will only receive audio-based standardized mindfulness practice instructions three times per week. The effects of MBI will be assessed based on the EMA data, right after the intervention and at the 2-month follow-up. The primary outcome will be participants’ psychological distress measured by the depression anxiety stress scale. The secondary outcomes will include participants’ subjective well-being, measured by the satisfaction with life scale, and level of resilience, measured by the psychological empowerment scale. Multilevel structural equational modelling will be applied to examine the pathways of the relationship between daily life events, cognitive appraisal, and psychological distress. DISCUSSION: The potential benefit of the proposed study is to increase the psychological well-being of parents of children with ASD, and the method may extend to participants suffering from other psychological issues in the future. Trial registration: This trial has been registered on clinicaltrials.gov with the ID of NCT05746468.

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11. Zhou Q, Lei Y, Du H, Tao Y. Public concerns and attitudes towards autism on Chinese social media based on K-means algorithm. Scientific reports. 2023; 13(1): 15173.

To investigate the hot topics and attitudes of autism in the larger community. In this study, we analyzed and summarized experimental texts from the social media platform Zhihu using the TF-IDF algorithm and K-means clustering approach. Based on the analysis of the 1,740,826-word experimental text, we found that the popularity of autism has steadily risen over recent years. Sufferers and their parents primarily discuss autism. The K-means clustering algorithm revealed that the most popular topics are divided into four categories: self-experience of individuals with autism, external views of individuals with autism, caring and stressful behaviors of caregivers, and information about autism. This study concluded that people with autism face more incredible negative emotions, external cognitive evaluations of the autistic group reflect stereotypes, the caregiver’s family suffers high financial and psychological stress, and disorders caused by disease in autistic individuals.

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